Clear cell renal cell carcinoma (RCC) is the most common renal tumor with an incidence of about 30,000 cases per year in the United States (Motzer et al., New Engl. J. Med. 335: 865-875 (1996)). For patients with metastatic RCC, the 5-year survival rate is approximately 10% because RCC is highly resistant to most chemotherapies (Motzer et al., J. Urol. 163: 408-417 (2000)). RCC has been considered immunogenic, and 10-20% of RCC patients with metastases can respond to cytokine-based therapy (e.g., interleukin (IL)-2 or IL-2 combined with interferon (IFN)-α) (Yang et al., J. Clin. Oncol. 21: 3127-3132 (2003); Tourani et al., J. Clin. Oncol. 21: 3987-3994 (2003)) with some of these patients appearing to be cured.
Despite the immunogenicity of RCC, there has been little progress in treating metastatic RCC patients with immunotherapy since the advent of IL-2 (Bleumer et al., Eur. Urol. 44: 65-75 (2003)). There have been major problems in defining the molecular basis of the immune response to RCC, in contrast to the rapid progress with human melanoma. This is largely due to a lack of a source of RCC-reactive T cells, again in contrast to melanoma, where IL-2 cultured tumor-infiltrating lymphocytes are often tumor reactive. Recently, Hanada et al. successfully generated a CD8+ T-cell clone from a patient with metastatic RCC, which recognized fibroblast growth factor (FGF)-5 (Hanada et al., Cancer Res. 61: 5511-5516 (2001); Hanada et al., Nature 427: 252-256 (2004)). FGF-5 proved to be one of a few RCC antigens that are suitable for clinical therapy because it is overexpressed in many tumors, but not in normal tissues. Yet, this remains only one of very few successful examples of generating RCC-reactive T cells by culturing TILs.
In view of the foregoing, there is a need in the art for RCC-reactive T cells for use in treating RCC patients. The invention provides such T cells and methods of treating cancer, especially RCC.